On January 13, FDA announced the availability of a new draft guidance document titled, Guidance for IRBs, Clinical Investigators, and Sponsors: IRB Continuing Review After Clinical Investigation Approval. Pursuant to FDA regulations 21 C.F.R. §§ 56.108(a) and 56.109(f), IRBs must have written procedures for, among other things, continuing reviews (at least annually) of IRB-approved clinical trials and determining which of those studies require more frequent review. The new guidance document outlines how IRBs can carry out these responsibilities and provides guidance on what information should be provided to the IRB to assist with continuing reviews. In 2006, FDA announced an initiative to update its 1998 Information Sheets, which provide guidance to IRBs, Sponsors, and Investigators. When finalized, the new guidance will supersede FDA’s Information Sheet, Continuing Review After Study Approval.

To assist IRBs with their reviews, the draft guidance document includes a list of information that FDA recommends IRBs consider during the continuing review, e.g., summaries of subject withdrawals, summaries of complaints, and the current version of the protocol and informed consent documents in use. For multi-center studies, “FDA recommends that sponsors provide IRBs directly with information from the entire study, data monitoring committee reports, and any other information about the test article.” FDA also states that IRBs may have written procedures to delegate among individual IRB members portions of the IRB continuing reviews so that the workload is sufficiently distributed to allow efficient review.

With regard to expedited procedures for continuing review, the document provides a discussion of two of the nine categories (published in the Federal Register, see63 Fed. Reg. 60353, 60356 (Nov. 9, 1998)) of research eligible for the expedited review set forth in 21 C.F.R. § 56.110(b). These two categories, categories (8) and (9), are the only categories that apply to continuing reviews. Category (8) provides for expedited continuing review where the research is permanently closed to new subjects, where no subjects have been enrolled and no additional risks have been identified, or where the remaining research is limited to data analysis. Category (9) provides for expedited review where the research is not being conducted under an investigation new drug (IND) application or an investigational device exemption (IDE), expedited review categories (2) through (8) do not apply to the research, and the IRB has documented “that the research involves no greater than minimal risk to the subjects and no additional risks have been identified.”

Pursuant to 21 C.F.R. §§ 56.108(a)(2) and 56.109(f), IRBs must determine the appropriate frequency of continuing reviews, i.e., identify studies that should be reviewed more frequently than annually. The guidance document provides a list of factors that FDA recommends IRBs consider when determining the frequency of reviews. These factors include the risks involved in the trials, vulnerability of the study population, experience of the investigators, the IRB’s history with the sponsor and/or investigator, and whether the studies involve novel therapies. FDA recommends that IRBs “establish written procedures for informing investigators of the FDA’s regulations and the IRB’s own policies and procedures on continuing review requirements.”

Other Clinical Trial-Related Developments:

On December 29, 2009, FDA announced a proposed rule that would amend the Agency’s informed consent regulations. The Food and Drug Administration Amendments Act (FDAAA) § 801(b)(3)(A) amended the Public Health Service (PHS) Act to require that FDA promulgate regulations that would require the informed consent forms for “applicable” clinical drug trials include a statement that clinical trial information has been or will be submitted to NIH/NLM for inclusion in the clinical trial registry databank (i.e., clinicaltrials.gov). Although FDAAA § 801(b)(3)(A) requires this change for applicable drug trials only, FDA’s proposed rule would extend the change in the informed consent form requirements to applicable device trials as well.

In October 2009, FDA announced the availability a guidance document titled, Guidance for Industry: Investigator Responsibilities - Protecting the Rights, Safety, and Welfare of Study Subjects. The guidance document provides information to investigators on how they can meet their responsibilities under 21 C.F.R. Parts 312 and 812 to both protect study participants and ensure the integrity of study data. The guidance document covers topics such as delegation of study-related tasks among the trial staff, training of trial staff, supervision of the trial, investigators’ oversight responsibilities, medical care made available to study participants, and investigator responsibilities towards protocol violations that represent unreasonable risks. This guidance document finalizes a draft guidance that was published in May 2007.